Mass spectrometers can employ one of several different methods for mass analysis, including time of flight (TOF). To date, most TOF analyzers have employed linear injection of ions from the ionization region into the mass analyzer. Disadvantages of this mode of operation include the addition of the kinetic energy distribution from the ionization process onto the energy imparted by the accelerating potential. Also, the neutral products from metastable or collisional decomposition can contribute to the background signal. New instruments (Mariner) are being developed by Perkin Elmer Biosystems to circumvent these problems. These employ electrospray ionization with collisional colling in a quadrupole lens followed by orthogonal acceleration into the TOF. We are working with Perkin Elmer to optimize the use of these instruments for a variety of analytical problems, using both direct infusion of samples and interfacing to capillary column HPLC. The TOF analyzer gives high resolution data and accurate mass measurements; we are developing algorithms to optimize the use of this information for peptide and protein analysis. (Additional effort and instrument time reported under Collaborative projects and other Technical Research and Development projects.)